Principal problems of collagen fiber formation are the assembly of the precusor molecule, procollagen, and its secretion from the cell. This is accompanied by cleavage to collagen and association of molecules to fibers. We shall investigate these successive processes with our recently developed methods, asking: how do the constituent polypeptide chains of procollagen come together, helically fold, and become altered by secondary modifications? We have found that the amino end of each procollagen peptide specifically recognizes the corresponding regions of the other two strands, and shall explore this problem of protein assembly in detail. Using embryonic bone, cartilage, aorta, and skin we shall look for biochemical mechanisms underlying the observed differences in collagen fiber structure in these different connective tissues. Thus we shall link the molecular processes of self assembly with the type and properties of the fiber systems. This will also be studied in cell culture, searching for intermediate stages of fiber formation and investigating the biochemical cooperation between cells and the connective tissue matrix which they make. The research has significance for developmental and molecular biology and for medicine. It is to see how the formation of a supramolecular structure, the collagen fibril, can be controlled by the cells which manufacture the components. The medical importance of correct and regulated collagen fiber development is in normal growth and development, wound healing, and the control of damage due to connective tissue diseases.